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Background: The Exercise interveNtion outdoor proJect in the cOmmunitY (ENJOY) Seniors Exercise Park program uses specialized outdoor equipment and a physical activity program to engage older people in physical activity, with multiple health benefits. We determined the cost-effectiveness of the ENJOY program. Methods: The economic evaluation compared health care utilization costs 6 months prior to and 6 months post ENJOY program participation. Incremental cost-utility analysis for the primary aim (quality of life) and incremental cost-effectiveness analysis for the secondary aim (falls) were used. Analyses took a societal perspective inclusive of Australian government-funded health care and pharmaceuticals in addition to hospitalizations, community-based nursing and allied health, and community services. Productivity costs were also calculated. Results: Fifty participants (average age 72.8 y [SD 7.4] and 78.0% [n = 39/50] women) were included. Participation in the ENJOY program reduced health care costs in the 6 months following the program: preintervention, $9764.49 (SD $26,033.35); postintervention, $5179.30 (SD $3826.64); observed postintervention reduction −$4.585.20 (95% confidence interval, −$12,113.99 to $2943.59; P = .227) without compromising quality of life (mean difference [MD] 0.011; 95% confidence interval, −0.034 to 0.056; P = .631) or increasing the likelihood of a fall (−0.5; 95% confidence interval, 0.00 to −0.50; P = .160). The ENJOY intervention is likely cost-effective. Conclusions: Planning for shared community spaces should consider the benefits of a Seniors Exercise Park as part of the built environment.

Background The physical environment has been shown to have a positive effect on the promotion of physical activity of older people. Outdoor environments that incorporate specialised exercise equipment suitable for older people are uniquely placed to promote physical activity and social connectedness amongst older people. The ENJOY project included the installation of specialised outdoor exercise equipment (the Seniors Exercise Park) and the delivery of a physical and social activity program for older people as part of a prospective pre-post research design. The installation of the specialised equipment in public sites and an aged care facility was also aimed at increasing usage of the equipment by older people from the wider community and to increase physical and social activities. Method A conceptual framework for implementation and several engagement methods were utilised to guide the research and to support the participating partners throughout the project. This paper is a reflective narrative describing the collaborative process and approach utilised to engage local governments and community, and reports the challenges and the lessons learnt to inform future strategies for implementation. Results The conceptual framework for the implementation process that guided the conduct and delivery of the ENJOY project included the core elements of the Interactive Systems Framework and the ecologic framework. These models incorporate elements of research-to-practice and community-centred implementation to accommodate the unique perspectives of a range of stakeholders. Conclusion Partner characteristics such as local governments’ structure and policy as well as community factors can impact on implementation. Partnership with local governments with effective communication, strategic planning and community and seniors engagement approaches are recommended for successful implementation. The lessons learnt can further assist public health research design around changes to the built environment to positively impact on older people’s physical activity levels. Trial registration Trial registration number ACTRN12618001727235. Date of registration 19th October 2018, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=375979

Objectives: Long-term engagement and participation in physical activity by older adults in the general population is poor. The Exercise interveNtion outdoor proJect in the cOmmunitY for older people (the ENJOY project) is a community-based research project utilizing an outdoor Seniors Exercise Park that demonstrated increased physical activity level as well as physical and mental health benefits. This study aims to explore participants’ perceptions about barriers and facilitators to ongoing participation as well as the usage pattern of the Seniors Exercise Park. Method: People aged ≥60 yr underwent a 12-wk structured supervised physical activity program using outdoor exercise park equipment followed by a 6-month maintenance phase. Participants completed two surveys: at the completion of the 12-wk structured supervised program and at the completion of the 6-month maintenance phase. Access to the Seniors Exercise Park was also electronically monitored during the maintenance phase. Results: The social aspect (60%), health benefits/improvement (41.5%), and supervision (36.9%) were the most cited factors in positively supporting participation, with 60.8% continued using the Exercise Park regularly during the maintenance phase. The main barriers to continued usage for both regular users and nonusers included other commitments (71.4%), the weather (60.7%), and medical/health problems (42.8%). Conclusions: The Seniors Exercise Park can be utilized to promote sustainable engagement in physical activity for older people. However, future implementation strategies should consider approaches to overcome barriers for participation.

Background While the underlying neuropathology of dementia is not curable, interventions and treatment, such as physical activity, can offer physical and functional gains leading to better mobility, independence and quality of life. The Seniors Exercise Park program is an evidence-based physical and social activity program using an innovative design in outdoor exercise equipment specifically designed for older people. This unique program has never been tested with older people living with dementia. This study will evaluate the feasibility of delivering the Seniors Exercise Park program for people living with mild to moderate dementia in residential aged-care. This study will identify the optimal physical activity program, evaluate the safety of equipment usage and determine optimal supervision needs. The potential physical, social, quality of life and cognitive benefits of participation in the Seniors Exercise Park program will also be examined. Methods This is a feasibility pilot randomised controlled design with pre-post evaluation. Adults aged ≥ 60 years who have symptoms of dementia and/or who have been diagnosed with dementia will be recruited from an aged-care facility in Melbourne. Participants allocated to the intervention group will undergo a 12-week structured supervised physical activity program using the outdoor Seniors Exercise Park equipment followed by a 12-week maintenance phase (unstructured physical activity). Participants will be assessed at baseline, 3 and 6 months. Participants allocated to the control group will attend activities provided by the aged-care facility. A sample of 12 participants per group is the targeted sample size. Feasibility will be evaluated in terms of recruitment rate, retention, attendance, overall adherence, dropout rate, adverse events, modifications to the exercise program delivery and supervision needs. A comprehensive suite of cognitive and health-related questionnaires and physical function measures will also be collected. Discussion The ENJOY program for independence in dementia will determine the suitability of the Seniors Exercise Park program for people diagnosed with mild to moderate dementia. Outcomes could inform future design of dementia-friendly built environments to increase physical activity participation for residential aged-care facilities. Trial registration This trial is registered with the Australian New Zealand Clinical Trials Registry—Registry Number ACTRN12620000733976. Registered on the 13th of July 2020.

This paper seeks to introduce readers to the regulation of immigration advice, and how this can work in practice in clinical legal education. The case study of Queen Mary Legal Advice Centre demonstrates that although the statute does not ideally seem to fit with the regulation of university law clinics, it is possible to be compliant. Far from being a negative aspect, regulation in these unique legal advice settings can actually provide a rich ethical learning environment and produce well rounded future lawyers.

Heavy oil extraction using steam flooding methods, such as steam assisted gravity drainage (SAGD), has been used for several decades; yet no severe corrosion damage has been reported despite the pr...

Background The number of falls experienced by people with knee osteoarthritis (OA) is almost double the number experienced by people with no OA. The neuromuscular elements required to arrest a fall are more impaired in people with knee OA compared to their asymptomatic counterparts. Therefore, these elements may need to be incorporated into an exercise intervention to reduce the risk of falling. The aim of this study will be to examine the feasibility, safety and patient satisfaction of a high-speed resistance-training program, with and without balance exercises, in people with knee OA compared to a control group. The effect of these exercise programs on lower-limb muscle strength and physiological and functional risk factors for falls will also be examined. Methods This study will be a pilot randomized controlled trial with a pre- and post-intervention design (outcome assessments at baseline and 8 weeks after participation commencement) comparing three groups: a control group (no intervention), a high-speed resistance-training group and a high-speed resistance-training plus balance exercises group. Thirty people with knee osteoarthritis aged 60–90 years will be recruited and randomized to one of the three groups. Feasibility and safety will be assessed by examining adherence to the exercise program, dropout rate, pain level during and following exercise, number of exercises stopped due to pain, and any adverse event or any incident that prevents the participant from completing the prescribed exercise. Secondary measures of lower-limb strength, physical function, self-reported pain and function, fear of falls, and executive function and quality of life will also be assessed. To determine statistical trends of effectiveness and hence to inform sample size for a fully powered study, analyses of the secondary outcomes will be performed to assess the changes within and between groups over time (pre-post) using repeated measure ANOVA. Discussion The results of this study will improve understanding of what type of exercise is safe and beneficial for people with knee OA to reduce their risk of falling, and hence will inform the development of a future large research trial. Trial registration Australian New Zealand Clinical Trials Registry, ID: ACTRN12616001382460. Registered on 6 October 2016. Electronic supplementary material The online version of this article (doi:10.1186/s13063-017-2129-7) contains supplementary material, which is available to authorized users.

Postmyocardial infarction (MI) rat myocytes demonstrated depressed Na+/Ca2+exchange (NCX1) activity, altered contractility, and intracellular Ca2+ concentration ([Ca2+]i) transients. We investigated whether NCX1 downregulation in normal myocytes resulted in contractility changes observed in MI myocytes. Myocytes infected with adenovirus expressing antisense (AS) oligonucleotides to NCX1 had 30% less NCX1 at 3 days and 66% less NCX1 at 6 days. The half-time of relaxation from caffeine-induced contracture was twice as long in ASNCX1 myocytes. Sarcoplasmic reticulum (SR) Ca2+-ATPase abundance, SR Ca2+uptake, resting membrane potential, action potential amplitude and duration, L-type Ca2+ current density and cell size were not affected by ASNCX1 treatment. At extracellular Ca2+ concentration ([Ca2+]o) of 5 mM, ASNCX1 myocytes had significantly lower contraction and [Ca2+]i transient amplitudes and SR Ca2+ contents than control myocytes. At 0.6 mM [Ca2+]o, contraction and [Ca2+]i transient amplitudes and SR Ca2+ contents were significantly higher in ASNCX1 myocytes. At 1.8 mM [Ca2+]o, contraction and [Ca2+]i transient amplitudes were not different between control and ASNCX1 myocytes. This pattern of contractile and [Ca2+]i transient abnormalities in ASNCX1 myocytes mimics that observed in rat MI myocytes. We conclude that downregulation of NCX1 in adult rat myocytes resulted in decreases in both Ca2+ influx and efflux during a twitch. We suggest that depressed NCX1 activity may partly account for the contractile abnormalities after MI.

The functional consequences of overexpression of rat heart Na+/Ca2+exchanger (NCX1) were investigated in adult rat myocytes in primary culture. When maintained under continued electrical field stimulation conditions, cultured adult rat myocytes retained normal contractile function compared with freshly isolated myocytes for at least 48 h. Infection of myocytes by adenovirus expressing green fluorescent protein (GFP) resulted in >95% infection as ascertained by GFP fluorescence, but contraction amplitude at 6-, 24-, and 48-h postinfection was not affected. When they were examined 48 h after infection, myocytes infected by adenovirus expressing both GFP and NCX1 had similar cell sizes but exhibited significantly altered contraction amplitudes and intracellular Ca2+concentration ([Ca2+]i) transients, and lower resting and diastolic [Ca2+]iwhen compared with myocytes infected by the adenovirus expressing GFP alone. The effects of NCX1 overexpression on sarcoplasmic reticulum (SR) Ca2+content depended on extracellular Ca2+concentration ([Ca2+]o), with a decrease at low [Ca2+]oand an increase at high [Ca2+]o.The half-times for [Ca2+]itransient decline were similar, suggesting little to no changes in SR Ca2+-ATPase activity. Western blots demonstrated a significant ( P ≤ 0.02) threefold increase in NCX1 but no changes in SR Ca2+-ATPase and calsequestrin abundance in myocytes 48 h after infection by adenovirus expressing both GFP and NCX1 compared with those infected by adenovirus expressing GFP alone. We conclude that overexpression of NCX1 in adult rat myocytes incubated at high [Ca2+]oresulted in enhanced Ca2+influx via reverse NCX1 function, as evidenced by greater SR Ca2+content, larger twitch, and [Ca2+]itransient amplitudes. Forward NCX1 function was also increased, as indicated by lower resting and diastolic [Ca2+]i.

The role of dynamics in modifying the response of the Arctic ice pack to inter-annually varying forcings and to climate perturbations is investigated using simulations from a two-dimensional ice model and a global climate model (GCM). Inter-annual variability in ice-covered area for 1985-93 is dominated by ice transport, and different transport regimes affect substantially the response of the ice pack to climate perturbations. The thermodynamic-only simulations are more sensitive to initial ice conditions, and respond less than the dynamk-thermodynamic model to small perturbations, but with a greater response to larger perturbations. Comparisons of GCM simulations that use different ice treatments highlights the importance of considering the distribution of ice thickness and extent in assessing climate-change responses.

The Na(+)/Ca(2+) exchanger gene NCX1 undergoes alternative splicing leading to several isoforms that differ in a small portion of the large cytoplasmic loop. This loop is involved in many regulatory processes of NCX1, including ionic regulation by the transported substrates Na(+) and Ca(2+). High intracellular Ca(2+) can alleviate intracellular Na(+)-dependent inactivation in exon A (NCX1.4)-containing isoforms but not in those containing the mutually exclusive exon B (NCX1.3). Giant excised patches from Xenopus oocytes expressing various NCX1 constructs were used to examine the specific amino acids responsible for these observed regulatory differences. Using a chimeric approach, the region responsible was narrowed down to the small central part of exon A (IDDEEYEKNKTF). Replacing the second aspartic acid of this sequence with arginine (the corresponding amino acid in exon B) in an exon A background completely prevented the effect of Ca(2+) on intracellular Na(+)-dependent inactivation. Mutating the second lysine to cysteine (exon B) had a similar, but only partial, effect. The converse double mutant, but neither single mutation alone, introduced into an exon B background (arginine to aspartic acid and cysteine to lysine) was able to restore the NCX1.4 regulatory phenotype. These data demonstrate that aspartic acid 610 and lysine 617 (using the rat NCX1.4 numbering scheme) are critical molecular determinants of the unique Ca(2+) regulatory properties of NCX1.4.

Objective: Apolipoprotein E (APOE) E4, apolipoprotein B-100 (APOB) Q3611 allele, the angiotensin converting enzyme (ACE) deletion (D) allele and glycoprotein IIIa (GP3A) P33 mutant allele are reported to predispose to early-onset coronary heart disease (CHD). These associations were not all confirmed in more recent studies. To determine the impact of these alleles on CHD, we examined the prevalence of these mutations in patients presenting with early-onset CHD and compared them to those manifesting CHD later in life. The delayed-onset was considered a sign of longevity and would serve as a comparative group to assess prevalence of the biochemical and genetic risk factors. Methods: 300 patients with a history of myocardial infarction or angina pectoris and angiographically documented CHD were studied. Patients were divided into two groups: group 1 (G1 = 150 patients) presenting with these findings under the age of 50 years; while group 2 (G2 = 150 patients) were patients presenting for the first time over the age of 65 years. Prevalence of the alleles of APOE, APOB, ACE and GP3A was assessed by molecular analysis. An association of any of these genotypes with early onset CHD could lead to a higher prevalence in the younger age group. Results and Conclusions: None of the suspected alleles namely APOB Q3611 [G1: 10.7% vs. G2: 9.0%, p = 0.57], ACE D (G1: 52.0% vs. G2: 49.7%, p = 0.57), or the GP3A P33 (G1: 17.3% vs. G2: 15.7%; p = 0.58) showed any significant difference between the two groups. Subjects with APOE E4 were more frequent in the younger age group (G1: 18.3% vs. G2: 13.7%; p = 0.047), while APOE E2 was more frequent in G2 (G2: 10.0% vs. G1: 2.7%; p = 0.0002). Multivariate analysis showed an odds ratio of APOE E2 allele in G1 of 0.27 with a confidence interval of 0.10–0.73.

Objective: In the presence of low serum folate, mutant 5,10-methylenetetrahydrofolate reductase (MTHFR+ [A223V/C677T]) in the homozygous state (+/+), may predispose to higher plasma homocysteine (tHct) levels and coronary artery disease (CAD). To determine the impact of this relationship on predisposition to early-onset CAD, we examined the prevalence of the mutation and plasma tHct in patients with early-onset CAD and compared them to patients manifesting CAD later in life. Methods: Three hundred patients with history of acute myocardial infarction or angina pectoris and angiographically documented CAD were studied. Patients consisted of two groups: group 1 (G1 = 150 patients) presenting with these findings under age 50; while group 2 (G2 = 150) presented for the first time over age 65 years. Prevalence of the MTHFR+ mutation was assessed by molecular analysis, and plasma tHct and folate were measured. An association of the +/+ genotype with early onset CAD could lead to its higher prevalence in the younger age group. Results: There was no significant difference in the frequency of the (+/+) genotype between the two groups (G1: 11.3% vs. G2: 11.3%). However, patients with the (+/+) genotype in both groups had higher tHct when plasma folate was below the mean value (G1: p < 0.0001 while G2: p < 0.01). Conclusion: The mutant MTHFR genotype was not found to be a determining factor in early-onset CAD. Higher tHct values were obtained in the older age group, which is expected because other studies have shown that tHct levels increase with age. A significant relation was shown between MTHFR genotype and low folate status yielding high tHct levels in those with the (+/+) genotype. As this relation was seen in both groups, although to a lesser extent in the older G2, it does not explain the underlying cause of early-onset CAD.

The stoichiometry with which the Na+/Ca2+ exchanger, NCX1, binds and transports Na+ and Ca2+ has dramatic consequences for ionic homeostasis and cellular function of heart mycocytes and brain neurons, where the exchanger is highly expressed. Previous studies have examined this question using native NCX1 in its endogenous environment. We describe here whole-cell voltage clamp studies using recombinant rat heart NCX1.1 expressed heterologously in HEK-293 cells. This system provides the advantages of a high level of NCX1 protein expression, very low background ion transport levels, and excellent control over clamped voltage and ionic composition. Using ionic conditions that allowed bi-directional currents, voltage ramps were employed to determine the reversal potential for NCX1.1-mediated currents. Analysis of the relation between reversal potential and external [Na+] or [Ca2+], under a variety of intracellular conditions, yielded coupling ratios for Na+ of 1.9–2.3 ions per net charge and for Ca2+ of 0.45±0.03 ions per net charge. These data are consistent with a stoichiometry for the NCX1.1 protein of 4 Na+ to 1 Ca2+ to 2 charges moved per transport cycle.